First breathing lung-on-chip developed using genetically identical cells

Amazing stuff!

"Researchers at the Francis Crick Institute and AlveoliX have developed the first human lung-on-chip model using stem cells taken from only one person. These chips simulate breathing motions and lung disease in an individual, holding promise for testing treatments for infections like tuberculosis (TB) and delivering personalized medicine. ...

Until now, these lung-on-chip devices have been made of a mixture of patient-derived and commercially available cells, meaning they can't fully replicate the lung function or disease progression of a single individual.

In the study, the team ... developed a new lung-on-chip model that contains only genetically identical cells derived from stem cells from a single donor. ...

To further simulate the human lung, AlveoliX has designed specialized machines to impose rhythmic three-dimensional stretching forces on the recreated air sac barrier, mimicking the motion of breathing. This stimulates the formation of microvilli, a key feature of alveolar epithelial cells, to increase surface area for lung functions ..."

"... Tuberculosis (TB) is a very slow-progressing disease in humans, taking months for a person to develop symptoms after being infected with the bacteria Mycobacterium tuberculosis. ... this highlights an increasing need to understand what’s happening in the early stages, when TB bacteria first encounter the body’s defences in the air sacs in the lungs. ..."

From the abstract (emphasis added):

"Immunocompetent and experimentally accessible alveolar systems to study human respiratory diseases are lacking.

Here, we developed a single-donor human induced pluripotent stem cell-derived lung-on-chip (iLoC) containing type II and I alveolar epithelial cells, vascular endothelial cells, and macrophages in a microfluidic device that mimic lung three-dimensional mechanical stretching and air-liquid interface.

Imaging and single-cell RNA sequencing analysis revealed that the iLoC recapitulated cellular profiles present in the human distal lung.
Infection of the iLoC with the human pathogen Mycobacterium tuberculosis (Mtb) showed that both macrophages and epithelial cells were infected but not permissive to bacterial replication. Stochastically, large macrophage clusters containing necrotic macrophages supporting Mtb replication were observed. A genetically engineered autophagy-deficient iLoC revealed that after Mtb infection, macrophage necrosis was higher upon ATG14 deficiency without bacterial replication. Together, we report an autologous, genetically tractable human alveolar model to study lung diseases and therapies."

First breathing 'lung-on-chip' developed using genetically identical cells

Built to breathe: mini ‘lungs’ recreate individual response to infection (original news release) "Lung-on-chip device exposes earliest stages of tuberculosis infection, and opens doors to investigate diversity in disease progression and personalised treatment. "

Autologous human iPSC–derived alveolus-on-chip reveals early pathological events of Mycobacterium tuberculosis infection (open access)

Image of the lung-on-chip, with cell nuclei in blue, macrophage in magenta, endothelial cells in yellow and tight junctions between epithelial and endothelial cells in white.

Image of a lung-on-chip infected by Mycobacterium tuberculosis, with cell nuclei in blue, dead macrophage in magenta, tight junctions between epithelial and endothelial cells in yellow and TB bacteria in white.

Fig. 1. iPSC-derived iAT2 and iAT1s are differentiated in a lung-on-chip microfluidic device.

Fig. 5. The iLoC mimic early stages of infection with Mtb.

A simple paper test could offer early cancer diagnosis for multiple cancers and metastasis

Good news! Cancer is history (soon)! This might be a breakthrough for cheap at home diagnostics for everyone!

What the article does not really describe is how the nanoparticles are introduced into the body or did I miss it?

" ... engineers have designed a new nanoparticle sensor that could enable early diagnosis of cancer with a simple urine test. The sensors, which can detect many different cancerous proteins, could also be used to distinguish the type of a tumor or how it is responding to treatment.

The nanoparticles are designed so that when they encounter a tumor, they shed short sequences of DNA that are excreted in the urine. Analyzing these DNA “barcodes” can reveal distinguishing features of a particular patient’s tumor. The researchers designed their test so that it can be performed using a strip of paper, similar to an at-home Covid test ...
In tests in mice, the researchers showed that they could use the sensors to detect the activity of five different enzymes that are expressed in tumors. They also showed that their approach could be scaled up to distinguish at least 46 different DNA barcodes in a single sample, using a microfluidic device to analyze the samples. ...
For this approach to work, the researchers had to use a chemical modification called phosphorothioate to protect the circulating DNA reporter barcodes from being broken down in the blood. This modification has already been used to improve the stability of modern RNA vaccines, allowing them to survive longer in the body. ...
The particles can be designed to carry many different DNA barcodes, each of which detects a different type of protease activity, which allows for “multiplexed” sensing. Using a larger number of sensors provides a boost in both sensitivity and specificity, allowing the test to more easily distinguish between tumor types. ... In tests in mice, the researchers showed that a panel of five DNA barcodes could accurately distinguish tumors that first arose in the lungs from tumors formed by colorectal cancer cells that had metastasized to the lungs. ...
This kind of testing could be used not only for detecting cancer, but also for measuring how well a patient’s tumor responds to treatment and whether it has recurred after treatment. ..."

From the abstract:

"Synthetic biomarkers, bioengineered sensors that generate molecular reporters in diseased microenvironments, represent an emerging paradigm in precision diagnostics. Despite the utility of DNA barcodes as a multiplexing tool, their susceptibility to nucleases in vivo has limited their utility. Here we exploit chemically stabilized nucleic acids to multiplex synthetic biomarkers and produce diagnostic signals in biofluids that can be ‘read out’ via CRISPR nucleases. The strategy relies on microenvironmental endopeptidase to trigger the release of nucleic acid barcodes and polymerase-amplification-free, CRISPR-Cas-mediated barcode detection in unprocessed urine. Our data suggest that DNA-encoded nanosensors can non-invasively detect and differentiate disease states in transplanted and autochthonous murine cancer models. We also demonstrate that CRISPR-Cas amplification can be harnessed to convert the readout to a point-of-care paper diagnostic tool. Finally, we employ a microfluidic platform for densely multiplexed, CRISPR-mediated DNA barcode readout that can potentially evaluate complex human diseases rapidly and guide therapeutic decisions."

A simple paper test could offer early cancer diagnosis | MIT News | Massachusetts Institute of Technology The new diagnostic, which is based on analysis of urine samples, could also be designed to reveal whether a tumor has metastasized.

CRISPR-Cas-amplified urinary biomarkers for multiplexed and portable cancer diagnostics (open access)

A new nanoparticle sensor that can enable cancer diagnosis with a simple urine test. The nanoparticles (blue) carry DNA barcodes (zigzag lines) that can be cleaved by cancer-associated proteases in the body (pac-man shapes). Once cleaved, the DNA barcodes can be detected in a urine sample.

Fig. 1: Engineering DNA-encoded synthetic urine biomarkers with CRISPR-Cas-mediated disease detection.

Sound can successfully remove microplastics from water

Good news! I blogged here several times now in the very recent past how plastic can be recycled or upcycled!

Could it even be that especially microplastics are actually fairly harmless? Is this noise about microplastics just another case of alarmism and hysteria? Quite possible!

If you suffer from plastophobia, please seek medical treatment immediately!

The article below also repeats this very dubious and most likely politically and  ideologically motivated statement: "A 2019 study revealed that we're even ingesting about 5 grams of microplastic, the weight of a credit card, each week."

"... A team of scientists out of Shinshu University has turned to sound to make it happen, experimenting with acoustic filtering to push MPs into a central channel, with branched sections filled by MP-free water that can be then released. ..."

From the abstract:

"Small plastic debris particles less than 5 mm in size called microplastics (MPs) are an emerging global ecological issue. This study developed a high enrichment microfluidic device to collect various-sized microparticles that uses four serial acoustic separations. To adopt the device for use with up to 200-µm MPs, the microchannel was widened by lowering the excitation frequency. The microfluidic device was designed for a 3.2-fold enrichment at each junction and a total 105-fold enrichment at the four junctions. The microfluidic network of the device was designed on the basis of a hydraulic-electric analogy and it worked even though only a single pump was used without multiple precise flow controllers. The collection performance of the device was evaluated based on the total collection rate that in turn was based on microscopic observations at the four junctions and the actual collection rate and the actual enrichment ratio obtained by measuring the effluents from the outlets. First, the device was evaluated separately using microparticles of 5, 10, 15, 25, 50, and 200 µm in diameter. The total collection rates were over 90% except for the 5-µm microparticles which seemed to be too small to manipulate acoustically at the lowered frequency. Finally, the device was evaluated with two example mixtures representing small MPs ranging from 200 µm down to 25 µm and very small MPs ranging from 25 µm down to 10 µm. Both the total collection rates and the actual collection rates ranged from 70% to 90%. However, the actual enrichment ratios ranged from half the designed value of 105 to the design value itself as some microparticles were slowed down and a few seemed to become trapped and attached to the microchannel walls by acoustic radiation force. Therefore, the microfluidic device was judged to be applicable to MP removal applications after prefiltration through a coarse mesh, while the MP analysis applications were judged to require improvement to inhibit the microparticle attachment used in 2D focusing. In conclusion, the serial acoustic separations could be a promising approach to highly enrich and remove various-sized MPs from environmental samples."

Sound can successfully remove microplastics from water

Filtering Pollution: A Microfluidic Device for Collecting Microplastics via Acoustic Focusing It has four serial trifurcated junctions where a 500 kHz acoustic wave is applied for a 105-fold enrichment of microplastics.

Microplastics (MPs), plastic debris smaller than 5 mm, indirectly harm the environment. They are traditionally collected and removed from water by filtering through meshes, which is inefficient. In this light, researchers from Japan have developed a high-enrichment microfluidic device that utilizes acoustic focusing to collect and remove 10–200 μm MPs from wastewater without recirculation. Its collection rates and enrichment ratios ranged approximately from 70–90% and 50–100, respectively on test samples.

A collection device for various-sized microparticles that uses four serial acoustic separations: Working toward microplastic emission prevention 

Graphical abstract

How electricity can heal skin wounds three times faster

Good news at least for e.g. the elderly or for diabetic patients or people with blood circulation issues suffering from chronic wounds!

"... Using a tiny engineered chip, the researchers were able to compare wound healing in artificial skin, stimulating one wound with electricity and letting one heal without electricity. The differences were striking. ...
In order to study exactly how this works for wounds, we developed a kind of biochip on which we cultured skin cells, which we then made tiny wounds in. Then we stimulated one wound with an electric field, which clearly led to it healing three times as fast as the wound that healed without electric stimulation," ..."

From the abstract:

"Upon cutaneous injury, the human body naturally forms an electric field (EF) that acts as a guidance cue for relevant cellular and tissue repair and reorganization. However, the direct current (DC) flow imparted by this EF can be impacted by a variety of diseases. This work delves into the impact of DC stimulation on both healthy and diabetic in vitro wound healing models of human keratinocytes, the most prevalent cell type of the skin. The culmination of non-metal electrode materials and prudent microfluidic design allowed us to create a compact bioelectronic platform to study the effects of different sustained (12 hours galvanostatic DC) EF configurations on wound closure dynamics. Specifically, we compared if electrotactically closing a wound's gap from one wound edge (i.e., uni-directional EF) is as effective as compared to alternatingly polarizing both the wound's edges (i.e., pseudo-converging EF) as both of these spatial stimulation strategies are fundamental to the eventual translational electrode design and strategy. We found that uni-directional electric guidance cues were superior in group keratinocyte healing dynamics by enhancing the wound closure rate nearly three-fold for both healthy and diabetic-like keratinocyte collectives, compared to their non-stimulated respective controls. The motility-inhibited and diabetic-like keratinocytes regained wound closure rates with uni-directional electrical stimulation (increase from 1.0 to 2.8% h−1) comparable to their healthy non-stimulated keratinocyte counterparts (3.5% h−1). Our results bring hope that electrical stimulation delivered in a controlled manner can be a viable pathway to accelerate wound repair, and also by providing a baseline for other researchers trying to find an optimal electrode blueprint for in vivo DC stimulation."

How electricity can heal wounds three times faster

Bioelectronic microfluidic wound healing: a platform for investigating direct current stimulation of injured cell collectives (open access)

Fig. 1 Microfluidic design to allow different electric field (EF) distributions around the wound

This self-driving microfluidic lab learns to make nanoparticles all on its own in a multi-step process

Amazing stuff! This is only the beginning! The potential is only limited by your imagination!

"The microfluidics platform called AlphaFlow employs a machine learning algorithm to design and optimize its own multi-step reaction sequences without human intervention. With this technology, AlphaFlow discovered a new way to make cadmium-based quantum dots that is better and much more efficient than the human-discovered synthesis, according to a recent study."

From the abstract:

"Closed-loop, autonomous experimentation enables accelerated and material-efficient exploration of large reaction spaces without the need for user intervention. However, autonomous exploration of advanced materials with complex, multi-step processes and data sparse environments remains a challenge. In this work, we present AlphaFlow, a self-driven fluidic lab capable of autonomous discovery of complex multi-step chemistries. AlphaFlow uses reinforcement learning integrated with a modular microdroplet reactor capable of performing reaction steps with variable sequence, phase separation, washing, and continuous in-situ spectral monitoring. To demonstrate the power of reinforcement learning toward high dimensionality multi-step chemistries, we use AlphaFlow to discover and optimize synthetic routes for shell-growth of core-shell semiconductor nanoparticles, inspired by colloidal atomic layer deposition (cALD). Without prior knowledge of conventional cALD parameters, AlphaFlow successfully identified and optimized a novel multi-step reaction route, with up to 40 parameters, that outperformed conventional sequences. Through this work, we demonstrate the capabilities of closed-loop, reinforcement learning-guided systems in exploring and solving challenges in multi-step nanoparticle syntheses, while relying solely on in-house generated data from a miniaturized microfluidic platform. Further application of AlphaFlow in multi-step chemistries beyond cALD can lead to accelerated fundamental knowledge generation as well as synthetic route discoveries and optimization."

This self-driving lab learns to make nanoparticles all on its own The machine learning–guided platform called AlphaFlow discovered and optimized a new synthesis for quantum dots

AlphaFlow: autonomous discovery and optimization of multi-step chemistry using a self-driven fluidic lab guided by reinforcement learning (open access)

Fig. 2: Overview of AlphaFlow

New protein purification method could make protein drugs cheaper

Good news! Impressive!

"One of the most expensive steps in manufacturing protein drugs such as antibodies or insulin is the purification step: isolating the protein from the bioreactor used to produce it. This step can account for up to half of the total cost of manufacturing a protein. ...
“This work uses bioconjugate-functionalized nanoparticles to act as templates for enhancing protein crystal formation at low concentrations,” ...
The researchers demonstrated that their approach can be used to crystallize lysozyme (an antimicrobial enzyme) and insulin. They believe it could also be applied to many other useful proteins, including antibody drugs and vaccines. ...
To create the surface they needed, the researchers coated gold nanoparticles with molecules called bioconjugates — materials that can help form links between other molecules. For this study, the researchers used bioconjugates called maleimide and NHS, which are commonly used for tagging proteins for study or attaching protein drugs to drug-delivering nanoparticles. ...
When solutions of proteins are exposed to these coated nanoparticles, the proteins accumulate at the surface and bind to the bioconjugates. Furthermore, the bioconjugates compel the proteins to align themselves with a specific orientation, creating a scaffold for additional proteins to come along and join the crystal. ..."

From the abstract:

"Although protein crystallization offers a promising alternative to chromatography for lower-cost protein purification, slow nucleation kinetics and high protein concentration requirements are major barriers for using crystallization as a viable strategy in downstream protein purification. Here, we demonstrate that nanoparticles functionalized with bioconjugates can result in an in situ template for inducing rapid crystallization of proteins at low protein concentration conditions. We use a microbatch crystallization setup to show that the range of successful crystallization conditions is expanded by the presence of functionalized nanoparticles. Furthermore, we use a custom machine learning-enabled emulsion crystallization setup to rigorously quantify nucleation parameters. We show that bioconjugate-functionalized nanoparticles can result in up to a 7-fold decrease in the induction time and a 3-fold increase in the nucleation rate of model proteins compared to those in control environments. We thus provide foundational insight that could enable crystallization to be used in protein manufacturing by reducing both the protein concentration and the time required to nucleate protein crystals."

New purification method could make protein drugs cheaper | MIT News | Massachusetts Institute of Technology MIT engineers find specialized nanoparticles can quickly and inexpensively isolate proteins from a bioreactor.

Enhancing Protein Crystal Nucleation Using In Situ Templating on Bioconjugate-Functionalized Nanoparticles and Machine Learning (open access)

A microfluidic device was designed to combine protein solution with nanoparticles and then form thousands of tiny, identical droplets. Inside each of these droplets, the proteins interact with the nanoparticles, which help them to form protein crystals.

Figure 1. (a) Schematic illustrating the concept of nanoparticle-assisted nucleation. (b) Conjugation of proteins to gold nanoparticles via the target amino acids. (c) Optical images of representative crystals obtained from vapor diffusion experiments with different nanoparticles.

Placenta-on-a-chip simulates nutrient transport between mother and foetus

When will we have a human on a chip? 😊

"Researchers ... have developed a “placenta-on-a-chip” that closely mimics the molecular exchange of nutrients between mother and foetus during pregnancy. ...  created the device using a pair of microfluidic channels, separated by an intricate network of hydrated fibres cultured on each side with different placental cells. The setup enabled the team to recreate disruptions to nutrient exchange caused by placental malaria, and could be a key step towards developing a treatment for the disease. ..."

From the abstract:

"... In this work, a placenta-on-a-chip model is developed to mimic the nutrient exchange between the fetus and mother under the influence of PM [placenta malaria]. In this model, trophoblasts cells (facing infected or uninfected blood simulating maternal blood and termed “trophoblast side”) and human umbilical vein endothelial cells (facing uninfected blood simulating fetal blood and termed “endothelial” side) are cultured on the opposite sides of an extracellular matrix gel in a compartmental microfluidic system, forming a physiological barrier between the co-flow tubular structure to mimic a simplified maternal–fetal interface in placental villi. The influences of infected erythrocytes (IEs) sequestration through cytoadhesion to chondroitin sulfate A (CSA) expressed on the surface of trophoblast cells, a critical feature of PM, on glucose transfer efficiency across the placental barrier was studied. ... The results demonstrated that CSA-binding IEs added resistance to the simulated placental barrier for glucose perfusion and decreased the glucose transfer across this barrier. The results of this study can be used for better understanding of PM pathology and development of models useful in studying potential treatment of PM."

Placenta-on-a-chip simulates nutrient transport between mother and foetus – Physics World

3D microfluidics-assisted modeling of glucose transport in placental malaria (open access)

Tissue model reveals key players in liver regeneration

Good news!

"The human liver has amazing regeneration capabilities: Even if up to 70 percent of it is removed, the remaining tissue can regrow a full-sized liver within months. ...
The new study, which appears this week in the Proceedings of the National Academy of Sciences, has identified one molecule that appears to play a key role, and also yielded several other candidates that the researchers plan to explore further. ...

One key factor is the reciprocal relationship between hepatocytes (the main type of cell found in the liver) and endothelial cells, which line the blood vessels. Hepatocytes produce factors that help blood vessels develop, and endothelial cells generate growth factors that help hepatocytes proliferate.

Another contributor that researchers have identified is fluid flow in the blood vessels. ...

To model all of these interactions ... designs microfluidic devices with channels that mimic blood vessels. To create these models of “regeneration on a chip,” the researchers grew blood vessels along one of these microfluidic channels and then added multicellular spheroid aggregates derived from liver cells from human organ donors. ...
Using this system, the researchers showed that increased fluid flow on its own did not stimulate hepatocytes to enter the cell division cycle. However, if they also delivered an inflammatory signal (the cytokine IL-1-beta), hepatocytes did enter the cell cycle. ..."

"Liver disease causes ∼2 million annual deaths, yet medical treatments and transplantable organs are both lacking. The liver can regenerate when mature hepatocytes divide, and while this process is well studied in rodents, parallel study of human biology has been impossible. We developed a microfluidic device that allows us to manipulate fluid flow, circulating cytokines, and/or paracrine interactions between liver and vascular cells, in order to model multicellular aspects of human liver regeneration. We found that physiologically relevant shear stresses increased the secretion of angiogenesis- and regeneration-associated factors, including prostaglandin E2 from endothelial cells, and induced primary human hepatocytes to enter the cell cycle. ..."

From the abstract:

"... To this end, we developed a three-dimensional (3D) platform called structurally vascularized hepatic ensembles for analyzing regeneration (SHEAR) to model multiple aspects of human liver regeneration. SHEAR enables control over hemodynamic alterations to mimic those that occur during liver injury and regeneration and supports the administration of biochemical inputs such as cytokines and paracrine interactions with endothelial cells. We found that exposing the endothelium-lined channel to fluid flow led to increased secretion of regeneration-associated factors. Stimulation with relevant cytokines not only amplified the secretory response, but also induced cell-cycle entry of primary human hepatocytes (PHHs) embedded within the device. Further, we identified endothelial-derived mediators that are sufficient to initiate proliferation of PHHs in this context. ..."

Tissue model reveals key players in liver regeneration | MIT News | Massachusetts Institute of Technology

A vascularized model of the human liver mimics regenerative responses (open access)

Human organ chips enable rapid drug repurposing for COVID-19

Recommendable! Amazing stuff! Microfluidics in action!

"A Wyss Institute-led collaboration spanning four research labs and hundreds of miles has used the institute’s organ-on-a-chip (Organ Chip) technology to identify the antimalarial drug amodiaquine as a potent inhibitor of infection with SARS-CoV-2, the virus that causes COVID-19.  ...
When tested in their more sophisticated microfluidic Lung Airway Chip, which had been infected with a pseudotyped SARS-CoV-2 virus, they found that most of these drugs, including hydroxychloroquine and chloroquine, were not effective. However, another antimalarial drug, amodiaquine, was highly effective at preventing viral entry. ...
The human Airway Chip that the Wyss team developed for these studies is a microfluidic device about the size of a USB memory stick that contains two parallel channels separated by a porous membrane. Human lung airway cells are grown in one channel that is perfused with air, while human blood vessel cells are grown in the other channel, which is perfused with liquid culture medium to mimic blood flow. Cells grown in this device naturally differentiate into multiple airway-specific cell types in proportions that are similar to those in the human airway, and develop traits observed in living lungs such as cilia and the ability to produce and move mucus. Airway Chip cells also have higher levels of angiotensin-converting enzyme-2 (ACE2) receptor protein, which plays a central role in lung physiology and is used by SARS-CoV-2 to infect cells."

Human organ chips enable rapid drug repurposing for COVID-19 – Harvard Gazette Emulating human lung airway in vitro identified helpful effects of antimalarial drug amodiaquine, now in clinical trials

Here is the underlying research article (dated 4/15/2020):

Human organs-on-chips as tools for repurposing approved drugs as potential influenza and COVID19 therapeutics in viral pandemics

Embedded droplet printing in yield-stress fluids

Good news! Amazing stuff!

"The discovery can transform a range of scientific applications including the study of biological and chemical processes, and can pave the way for more exquisite and targeted pharmaceutical and consumer products."

"Conventional microfluidic methods primarily rely on fluids that behave in simple ways, like water. Yield-stress fluids are materials that behave in a complex way, dramatically transitioning between solid-like and liquid-like behavior, depending on an applied stress. We introduce embedded droplet printing—a system for the generation and manipulation of fluid droplets within yield-stress fluids."


SMART announces new method for processing fluid droplets | MIT News: Researchers at the Singapore-MIT Alliance for Research and Technology and the National University of Singapore have developed a unique method for generating and processing fluid droplets under previously unattainable conditions. Microfluidics enables researchers to create unique environment for developing medicine, paving the way for more potent, high-quality drugs.


Embedded droplet printing in yield-stress fluids

Building Synthetic Cells From Scratch

Posted: 1/5/2019

Trigger

Just read this long, fascinating, and in depth article How biologists are creating life-like cells from scratch Built from the bottom up, synthetic cells and other creations are starting to come together and could soon test the boundaries of life. published by Nature Journal on 11/7/2018

To build synthetic cells from the bottom up has been one of the hot frontiers in science for about the past two decades!

European Advances

Surprise, surprise European scientists appear to be at the cutting edge in this field. “In September [of 2018], the US National Science Foundation (NSF) announced its first programme on synthetic cells, funded to the tune of $10 million.” What a late comer to the game! Whereas “... several European investigators ... have proposed building a synthetic cell as one of the European Commission’s Future and Emerging Technologies Flagship schemes, which receive funding of €1 billion.”

Within A Decade

Some scientists predict that we will have functioning synthetic cells created from molecules or other basic ingredients within a decade. We may even achieve industrial scale by then.

Artificial Mitochondria

Without energy synthetic cells would not work very well. “Joachim Spatz’s group at the Max Planck Institute for Medical Research in Heidelberg, Germany, has built a rudimentary mitochondrion that can create ATP inside a vesicle.” In order to do this, they used latest microfluidic technologies.

More Efficient Photosynthesis

According to this article, scientists are already working replicating photosynthesis. Photosynthesis could be an energy source of the future.

“Another Max Planck [Institute for Terrestrial Microbiology] synthetic-biology group ... has been chipping away at other approaches to constructing cellular metabolic pathways. ... pathways that allow photosynthetic microbes to pull carbon dioxide from the environment and make sugars and other cellular building blocks. ...

His group sketched out a system design that could convert CO2 into malate, a key metabolite produced during photosynthesis. ... team searched databases for enzymes that might perform each of the reactions. For a few, they needed to tweak existing enzymes into designer ones.

In the end, they found 17 enzymes from 9 different organisms, including E. coli, an archaeon, the plant Arabidopsis and humans. The reaction, perhaps unsurprisingly, was inefficient and slow7. ... After some further enzyme engineering, … operates 20% more efficiently than photosynthesis. Expanding this work, [team] has begun constructing a crude version of a synthetic chloroplast ...”

As an aside: About four years ago it was shown that quantum mechanics explains the efficiency of photosynthesis (see e.g. here). How will this research of synthetic photosynthesis and quantum effects work out?

Programmable Bioreactors

“... at the University of Minnesota in Minneapolis is working on ways to build programmable bioreactors, by introducing simple genetic circuits into liposomes and fusing them together to create more-complex bioreactors. ...

builds these bioreactors using a spinning tube system ... which produces smaller liposomes. The researchers add circles of DNA called plasmids that they have designed to perform a particular function, along with all the machinery needed to make proteins from DNA.”

Minimal Genome

The J. Craig Vintner Institute (JCVI) “... took one of the smallest-known microbial genomes on the planet, that of the bacterium Mycoplasma mycoides, and systematically disrupted its genes to identify the essential ones. Once they had that information, they chemically stitched together a minimal genome in the laboratory.

This synthesized genome contained 473 genes — about half of what was in the original organism — and it was transplanted into a related bacterial species, Mycoplasma capricolum. In 2016, the team showed that this minimal synthetic genome could ‘boot up’ a free-living, although slow-growing organism … As a next step, and supported by an NSF grant of nearly $1 million, ... will attempt to install the JCVI-syn3.0a genome into a synthetic liposome containing the machinery needed to convert DNA into protein, to see whether it can survive. … JCVI has been doing adaptive laboratory evolution experiments with JCVI-syn3.0a, selecting for organisms that grow faster in a nutrient-rich broth. So far, after about 400 divisions, ... have obtained cells that grow about 15% faster than the original organism. ... a handful of gene-sequence changes popping up. But there’s no evidence yet of the microbe developing new cellular functions or increasing its fitness by leaps and bounds.”